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Galantamine is a common medication used by people with Alzheimer’s disease and other forms of dementia around the world to treat their symptoms. Unfortunately, synthesizing the active compounds in a lab at the scale needed isn’t commercially viable. The active ingredient is extracted from daffodils through a time-consuming process, and unpredictable factors, such as weather and crop yields, can affect supply and price of the drug.
Now, researchers at The University of Texas at Austin have developed tools — including an artificial intelligence system and glowing biosensors — to harness microbes one day to do all the work instead.
In a paper in Nature Communications, researchers outline a process using genetically modified bacteria to create a chemical precursor of galantamine as a byproduct of the microbe’s normal cellular metabolism. Essentially, the bacteria are programmed to convert food into medicinal compounds.
“The goal is to eventually ferment medicines like this in large quantities,” said Andrew Ellington, a professor of molecular biosciences and author of the study. “This method creates a reliable supply that is much less expensive to produce. It doesn’t have a growing season, and it can’t be impacted by drought or floods.”
Danny Diaz, a postdoctoral fellow with the Deep Proteins research group in UT’s Institute for Foundations of Machine Learning (IFML), developed an AI system called MutComputeX that is key to the process. It identifies how to mutate proteins inside the bacteria to improve their efficiency and operating temperature in order to maximize production of a needed medicinal chemical.
“This system helped identify mutations that would make the bacteria more efficient at producing the target molecule,” Diaz said. “In some cases, it was up to three times as efficient as the natural system found in daffodils.”
The process of harnessing microbes to produce useful byproducts is nothing new. Brewers use yeast to make alcohol, and bacteria help create cheese and yogurt. Microbial fermentation is currently used to make certain types of insulin for diabetes treatment, hormones and recombinant proteins used in several drugs such as autoimmune treatments, and even vaccines. But applying AI in the process is relatively new and expands what is possible with microbial fermentation.

The research team genetically modified E. coli to produce 4-O’Methyl-norbelladine, a chemical building block of galantamine. The complex molecule is in a family of compounds extracted from daffodils that have medicinal uses in treating conditions such as cancer, fungal infections and viral infections, but using microbial fermentation to create a chemical in this family is new.
The scientists also created a fluorescent biosensor to quickly detect and analyze which bacteria were producing the desired chemicals and how much. When the biosensor, a specially created protein, comes into contact with the chemical researchers wanted to create, it glows green.
“The biosensor allows us to test and analyze samples in seconds when it used to take something like five minutes each,” said Simon d’Oelsnitz, a postdoctoral researcher formerly at UT Austin and now at Harvard University, the first author of the paper. “And the machine learning program allows us to easily narrow candidates from tens of thousands to tens. Put together, these are really powerful tools.”
Wantae Kim, Daniel Acosta, Tyler Dangerfield, Mason Schechter, James Howard, Hannah Do, James Loy, Hal Alper and Y. Jessie Zhang of UT and Matthew Minus of Prairie View A&M University were also authors of the paper. The research was supported by the National Institute of Standards and Technology, the Air Force Office of Scientific Research and the National Institutes of Health, and the National Science Foundation supports IFML. Computing resources were provided by Advanced Micro Devices.
Those involved in this research have submitted required financial disclosure forms with the University, and Ellington, Diaz and d’Oelsnitz have filed a patent application on materials described in this text. Diaz and d’Oelsnitz are each involved with startups related to this research.

In the wake of the COVID-19 pandemic, scientists have been racing to develop effective treatments and preventatives against the virus. A recent scientific breakthrough has emerged from the work of researchers aiming to combat SARS-CoV-2, the virus responsible for COVID-19.
Led by Jin Kim Montclare and her team, the study focuses on the design and development of a novel protein capable of binding to the spike proteins found on the surface of the coronavirus. The goal behind this innovative approach is twofold: first, to identify and recognize the virus for diagnostic purposes, and second, to hinder its ability to infect human cells.
The engineered protein, resembling a structure with five arms, exhibits a unique feature — a hydrophobic pore within its coiled-coil configuration. This feature enables the protein not only to bind to the virus but also to capture small molecules, such as the antiviral drug Ritonavir.
Ritonavir, already utilized in the treatment of SARS-CoV-2 infections, serves as a logical choice for integration into this protein-based therapeutic. By incorporating Ritonavir into the protein, the researchers aim to enhance the treatment’s efficacy while simultaneously targeting the virus directly.
The study marks a significant advancement in the fight against COVID-19, showcasing a multifaceted approach to combating the virus. Through a combination of protein engineering and computational design, the team has devised a promising strategy that may revolutionize current treatment modalities.
Although the research is still in its early stages, with no human or animal trials conducted as yet, the findings offer a proof of principle for the therapeutic potential of the designed protein. The team has demonstrated its ability to enhance the protein’s binding affinity to the virus spike protein, laying the groundwork for future investigations.
The potential applications of this protein-based therapeutic extend beyond COVID-19. Its versatility opens doors to combating a range of viral infections, offering a dual mode of action — preventing viral entry into human cells and neutralizing virus particles.
Furthermore, the success of this study underscores the importance of computational approaches in protein design. By leveraging computational tools such as Rosetta, the researchers have accelerated the process of protein engineering, enabling rapid iterations and optimization.
The development of this novel protein represents a significant step forward in the ongoing battle against COVID-19. As research progresses, the integration of computational design and protein engineering holds promise for the development of innovative therapeutics with broad-spectrum antiviral capabilities. While challenges remain, this study offers hope for a future where effective treatments against emerging viral threats are within reach.

After the egg has been fertilized by a sperm, the surrounding egg coat tightens, mechanically preventing the entry of additional sperm and the ensuing death of the embryo. This is according to a new study led by researchers at Karolinska Institutet and published in the journal Cell. The work also explains how mutations in egg coat proteins can cause female infertility and may eventually lead to new contraceptive methods.
Fertilization in mammals begins when a sperm attaches to the egg coat, a filamentous extracellular envelope that sperm must penetrate in order to fuse with the egg. Now an international team of researchers has mapped in detail the structure and function of the protein ZP2, an egg coat filament component that plays a key role in regulating how egg and sperm interact with each other at fertilization.
“It was known that ZP2 is cleaved after the first sperm has entered the egg, and we explain how this event makes the egg coat harder and impermeable to other sperm,” says Luca Jovine, Professor at the Department of Biosciences and Nutrition, Karolinska Institutet, who led the study. “This prevents polyspermy — the fusion of multiple sperm with a single egg — which is a fatal condition for the embryo.”
The changes in the egg coat after fertilization are also crucial to female fertility by ensuring the protection of the developing embryo until this implants in the uterus. The new knowledge may therefore have implications for the development of non-hormonal contraceptives that interfere with the formation of the egg coat. Moreover, the study explains egg coat-associated forms of female infertility.
“Mutations in the genes encoding egg coat proteins can cause female infertility, and more and more such mutations are being discovered,” explains Luca Jovine. “We hope that our study will contribute to the diagnosis of female infertility and, possibly, the prevention of unwanted pregnancies.”
Importantly, the study also shows that a part of ZP2 that was previously thought to act as a receptor for sperm is not necessary for sperm to attach to the egg. This raises the question of what is the true sperm receptor on the egg coat, which the researchers plan to investigate further.
The researchers combined X-ray crystallography and cryo-EM to study the 3D structure of egg coat proteins. The interaction between sperm and eggs carrying mutations in the ZP2 protein was functionally studied in mice, while the AI program AlphaFold was used to predict the structure of the egg coat in humans.
The study was carried out in collaboration with Osaka and Sophia universities in Japan and the University of Pittsburgh, USA, using data collected at SciLifeLab and the ESRF, DLS and BESSY II synchrotrons.
The research was mainly funded by the Knut and Alice Wallenberg Foundation, the Swedish Research Council and the Centre for Innovative Medicine (CIMED). There are no reported conflicts of interest.

Autophagy is a process used by cells as a recycling system to transport and break down organelles and other cytosolic components, which become enveloped in a membrane called the autophagosome (Fig 1). When this involves the removal of damaged mitochondria, commonly called the “powerhouse” of the cell, it is known as mitophagy. In a recent article published in The EMBO Journal, a team led by researchers at Tokyo Medical and Dental University (TMDU) elucidated the molecular details of how an enzyme called Tank-binding kinase 1 (TBK1) participates in a disease-relevant mitophagy mechanism.
Although autophagy has been characterized as a more general process meant to degrade and clear various cellular components, recent data have suggested that certain pathways are specifically involved in the autophagy of particular organelle types that are damaged or no longer needed. The researchers became interested in mitophagy mediated by molecules called PINK1 and Parkin, as they are proteins that have been pathologically linked to Parkinson’s disease.
“Mitophagy-related defects have been directly implicated in the neurodegeneration observed in Parkinson’s disease patients,” says Koji Yamano, lead author of the study. “Normally, PINK1 and Parkin work together to mark damaged mitochondria for removal by adding a chain of molecules called ubiquitin. This mark allows proteins called autophagy adaptors to associate with the mitochondria and bring in the autophagy machinery for autophagosome development.”
Although TBK1 is known to participate in PINK1/Parkin-mediated mitophagy, a detailed mechanism how it activates remained unclear. Using various molecular biology techniques, the team found that deleting the gene encoding TBK1 prevented association of an autophagy adaptor called optineurin (OPTN) during Parkin-mediated mitophagy (Fig 2). Additionally, deleting the OPTN gene prevented autophosphorylation of TBK1, which is necessary for it to function.
Further work suggested that the interactions between OPTN and ubiquitin, as well as between OPTN and the developing autophagosome, were all needed for OPTN and TBK1 to come together at the contact site between damaged mitochondria and the pre-autophagosome membrane. Without this contact site, TBK1 autophosphorylation could not occur.
The researchers also generated molecules called monobodies in their lab that could specifically bind OPTN and inhibit its physical interactions. The monobodies prevented OPTN accumulation at the mitophagy contact sites (Fig 3A). This subsequently blocked TBK1 activation (Fig 3B) and thereby mitochondrial degradation. These experiments further emphasized the importance of the OPTN-TBK1 relationship to support proper mitophagy.
“Because PINK1 and Parkin are critical contributors to the molecular basis of Parkinson’s disease, understanding the mechanistic details related to the mitophagy process mediated by these molecules is very important,” explains Yamano.
This study demonstrates a positive and reciprocal relationship between OPTN and TBK1 that is necessary for autophagosomes to begin forming on damaged mitochondria. The impactful finding may lead to the development of novel drugs to treat Parkinson’s disease.

Antibody responses to new SARS-CoV-2 variant infections and vaccinations are powerfully shaped by prior exposures to earlier SARS-CoV-2 vaccines, according to a new study from the Perelman School of Medicine at the University of Pennsylvania.
In the study, published today in Immunity, the researchers analyzed antibody responses in people infected with or vaccinated against the relatively new SARS-CoV-2 variants BA.5 and XBB. They found that even though BA.5 and XBB are very different from the original “ancestral” version of SARS-CoV-2, the responses to these newer variants came almost entirely from the B cell repertoire that was already in place due to prior vaccinations against the ancestral strain.
The good news is that these responses efficiently prevented BA.5 and XBB variants from infecting cells, which likely explains why BA.5 and XBB boosters protect recipients against severe illness from these new variants. Yet the findings underscore the power of an initial viral exposure, like from the initial SARS-CoV-2 vaccines, to shape immune responses to new variants even years later.
“Detailing how SARS-CoV-2 immune history influences the antibody response to new variants, through studies such as this one, will ultimately help us design more effective vaccines,” says study co-senior author Scott Hensley, PhD, a professor of Microbiology at Penn Medicine.
The study’s other co-senior author was E. John Wherry, MD, PhD, the Richard and Barbara Schiffrin President’s Distinguished Professor, Director of the Institute for Immunology, and Chair of the Department of Systems Pharmacology & Translational Therapeutics at Penn Medicine.
The study’s central finding was that, despite the many differences between BA.5 and XBB and the ancestral variant, antibody responses to these newer variants — even with multiple exposures — almost always targeted sites on the virus that had not changed since the ancestral version of the virus. In individuals with exposures to XBB — the more mutationally “distant” variant — the researchers did detect low numbers of antibodies that hit XBB-specific sites. The immune responses to the variants were highly dependent on the original B cell repertoire induced by the ancestral SARS-CoV-2 strain — and on the ability of those cells to cross-react with BA.5 and XBB variants.
The researchers found that individuals who initially had lower numbers of B cells elicited by the ancestral variant were more likely to produce totally new, variant-specific antibodies. More importantly, the researchers found that people who had high numbers of B cells against the ancestral SARS-CoV-2 strain were more likely to mount effective immune responses, which were mostly cross-reactive, to the BA.5 and XBB variants.

The phenomenon in which an initial antibody response to a virus dominates and delimits the response to later strains of the same virus is called “immunological imprinting,” or “original antigenic sin.” It has been described for decades, mostly in relation to influenza virus infections. One concern is that imprinting could potentially blunt the immune responses against newer virus strains in people with histories of exposure to prior strains. Given the striking ability of SARS-CoV-2 to evolve new variants, researchers have begun to detail imprinting’s effects in the SARS-CoV-2 context.
In the study, the researchers examined imprinting’s effects on antibody responses to SARS-CoV-2’s BA.5 and XBB variants. The two highly transmissible variants began circulating in 2022 and contain many changes from the original ancestral SARS-CoV-2 virus. Booster vaccinations against these variants were introduced in 2022 and 2023.
“Prior vaccinations are highly beneficial for establishing memory B cells that can be rapidly recruited to produce neutralizing antibodies against new SARS-CoV-2 variants,” Hensley says.
The main implication of the findings, according to the researchers, is that immunological imprinting from the original ancestral SARS-CoV-2 strain has a significant impact on the antibody responses to the BA.5 and XBB variants and boosters based on them. Those responses still appear to be protective, but it is unclear that that protection will remain robust as SARS-CoV-2 variants continue to evolve. Thus, the researchers say, the effect of immune imprinting on SARS-CoV-2 responses should continue to be monitored with further studies.
“Most people alive today have been immunologically imprinted by ancestral SARS-CoV-2, but that will inevitably change as time goes on,” Hensley says, “We need to continue studying how different prior exposures impact immunity to new variants that come down the road, and how this immunity affects viral evolution.”
Support for the study was provided by the National Institutes of Health (75N93021C00015, U19AI082630, AI105343, AI108545, AI155577, AI149680), the Parker Institute for Cancer Immunotherapy, the Burroughs Wellcome Fund and the Boehringer Ingelheim Fonds.

Television dramas can make criminal investigations look easy. In real life, DNA testing can be challenging and requires expensive equipment, special facilities and extensive training to identify DNA from a crime scene and determine which belongs to a potential suspect and which may have been transferred from someone who was never there. Research from the University of New Hampshire has found a less expensive and easier to use test to learn more about forensic touch DNA. This research has important implications for forensic investigations and being able to identify DNA from a primary contact — someone who may have committed the crime — as well as secondary DNA that was inadvertently and indirectly transferred through touch.
“So-called ‘touch DNA’ is a form of trace DNA that is deposited when a person touches something and leaves behind their skin cells, sweat or other fluids that contain their DNA,” said Samantha McCrane, a lecturer in anthropology and co-director of UNH’s Forensic Anthropology Identification and Recovery (FAIR) Lab. “While touch DNA is often the result of direct contact, which we call primary transfer, it can also be indirectly transferred between surfaces or individuals, leaving behind secondary or even tertiary DNA.”
In their study, recently published in the Journal of Forensic Sciences, researchers developed an innovative test that uses a more accessible and affordable sequence method, known as qPCR. To test their protocol, they paired male and female volunteers and kept it simple, only looking at one marker to determine the sex of the DNA. In the trials, they first had a male participant hold a gun grip for 30 seconds before placing it down on a sterilized table. Then, a female picked up the same gun grip and held it for 30 seconds and followed that by grasping a coffee cup for 30 seconds. Afterward, the gun grip, coffee mug and female’s hand were all swabbed for DNA.
The findings with the new method found male and female DNA on the gun grip in 71% of the trials indicating primary transfer since both participants directly touched the gun grip. Male DNA was found on the female’s hand in 50% of the trials representing secondary transfer since the DNA was transferred indirectly from the gun grip. Male DNA on the coffee mug was recorded 27% of time indicating tertiary, or third level, transfer since the DNA was indirectly transferred from the gun grip to the female’s hand and finally to the coffee mug.
“The challenge with transfer DNA is that it opens up the dangerous possibility of DNA ending up on items or victims at a crime scene that a person may not have touched,” said McCrane. “This has occurred in multiple cases, leading to innocent individuals being charged for crimes they didn’t commit.”
The study also looked at the potential effects of age, ethnicity and skin conditions on DNA transfer. Ethnicity and age did not appear to affect touch DNA deposits and the small sample of those with sloughing skin conditions, like eczema, did not show any significant association with primary DNA transfer.
Researchers say even DNA experts cannot distinguish between different types of DNA transfer and this understudied field lacks enough data to fully understand which variables affect direct versus indirect DNA transfer and how often it happens. These new study results contribute to a better understanding of the conditions under which secondary and tertiary DNA transfer occurs and researchers are hopeful this new inexpensive protocol could lead to more research allowing for greater sample sizes and replication runs.
Co-author on the study was Connie Mulligan, professor of anthropology at the University of Florida.

Published19 hours agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesBy Jim ReedHealth reporterThousands of people in the UK were infected with HIV and hepatitis C after being given contaminated blood products during the 1970s and 1980s.A public inquiry into what has been called the biggest treatment disaster in NHS history will publish its findings in May, but victims are still campaigning for compensation.Who was affected by the infected blood scandal and how many patients were involved?Two main groups of NHS patients were caught up in the scandal.Firstly, haemophiliacs – and those with similar disorders – who have a rare genetic condition which means their blood does not clot properly. People with haemophilia A have a shortage of a clotting agent known as Factor VIII. People with haemophilia B don’t have enough Factor IX. In the 1970s, a new treatment was developed to replace the missing clotting agents, made from donated human blood plasma. But whole batches of the replacement Factor VIII and IX products were contaminated with deadly viruses.The infected blood inquiry estimates that 1,250 people with bleeding disorders in the UK developed both HIV and hepatitis C as a result, including 380 children. Around two-thirds later died of Aids-related illnesses. Some of those infected unintentionally gave HIV to their partners.Another 2,400 to 5,000 people developed hepatitis C on its own, which can cause cirrhosis and liver cancer. This video can not be playedTo play this video you need to enable JavaScript in your browser.The second group of patients were given a contaminated blood transfusion after childbirth, surgery or other medical treatment between 1970 and 1991.Estimating the size of this group is difficult, but the inquiry thinks up to 100 may have been infected with HIV, and between 21,000 and 39,000 with hepatitis C.Tainted blood: The woman who lost two husbandsThe secret in my bloodITV to make drama about contaminated blood scandalWhy did the infected blood scandal happen?In the 1970s, the UK was struggling to meet the demand for blood-clotting treatments, so imported supplies from the US. But much of the blood was bought from high-risk donors such as prison inmates and drug-users. Factor VIII was made by pooling plasma from tens of thousands of donors.If just one was carrying a virus, the entire batch could be contaminated.UK blood donations were not routinely screened for hepatitis C until 1991, 18 months after the virus was first identified in a laboratory.Image source, Jackie BrittonWhat did the authorities know about infected blood?By the mid-1970s, there were repeated warnings that imported US Factor VIII carried a greater risk of viral infection. But attempts to make the UK more self-sufficient in blood products in the following years failed, so the NHS continued to use foreign supplies. Campaigners say haemophiliacs could have been offered an alternative treatment called Cryoprecipitate. This was less effective and harder to administer, but was made from the blood plasma of a single donor, lowering the infection risk. As late as November 1983, the government insisted there was no “conclusive proof” that HIV could be transmitted in blood, a line robustly defended by former health minister Ken Clarke when he appeared before the inquiry. By April 1985, all Factor VIII products were heat-treated to kill the HIV virus.This video can not be playedTo play this video you need to enable JavaScript in your browser.When was the infected blood inquiry set up and when will it report? The UK-wide infected blood inquiry was announced in 2017 after years of campaigning by victims. It was led by former judge Sir Brian Langstaff, and took evidence between 2019 and 2023. The inquiry will publish its report on 20 May. It had been expected in autumn 2023, but Sir Brian said more time was needed to prepare “a report of this gravity”.Who gave evidence to the inquiry?One of the first to take the stand was Derek Martindale, who has haemophilia. He was diagnosed with HIV and given a year to live in 1985, aged 23. He survived but his brother – who was also infected with HIV – did not. The inquiry also heard harrowing testimony from former pupils at Treloar’s, a specialist boarding school in Hampshire, where dozens of young haemophiliacs were infected with HIV. Specialist haemophilia doctors working at the time also gave evidence. As well as Lord Clarke, the inquiry heard from former and current ministers in all four UK nations, including Prime Minister Rishi Sunak and Chancellor Jeremy Hunt.Five things we’ve learned from the inquiryWill victims of the infected blood scandal get compensation?Those infected have received annual financial support from the government, but a final compensation deal has not been agreed. In late 2022, following advice from the inquiry, the government made interim payments of £100,000 each to around 4,000 surviving victims and some bereaved partners. In April 2023, Sir Brian said interim compensation should also be offered to the children and parents of those infected. He also recommended a final compensation scheme be set up, with the total cost likely to run into billions.The government said it would be “inappropriate” to consider final compensation payments ahead of the inquiry’s full report. What happened in other countries which were affected by inflected blood?Many other countries were affected by the same scandal, although some – including Finland – were self-sufficient in Factor VIII, which minimised HIV infections.In the US, companies that supplied infected products have paid out millions of dollars in out-of-court settlements.Politicians and drug companies have been convicted of negligence in other countries, including France and Japan. In his evidence to the inquiry, former health secretary Andy Burnham suggested there may be grounds for charges of corporate manslaughter in the UK.Related Internet LinksInfected Blood inquiryThe BBC is not responsible for the content of external sites.

Published53 minutes agoShareclose panelShare pageCopy linkAbout sharingImage source, Getty ImagesChanging how children are measured for obesity to a new system could be more accurate, a study has concluded.It revealed the traditional method of using Body Mass Index (BMI) is not as useful in measuring fat as waist-to-height ratio (WHtR). Over a 15-year follow-up, 7,237 nine-year-old children were studied.The findings could change guidelines that recommend BMI as a measure. Researchers said it was critical to accurately detects obesity in children.The Bristol project, the Avon Longitudinal Study of Parents and Children (ALSPAC), was published in the journal Paediatric Research.Obesity rates rose sharply among 10 and 11 year olds in England during the Covid pandemic and have not returned to pre-pandemic levels.Professor Julian Hamilton-Shield, a consultant paediatrician at the Bristol Royal Hospital for Children, said his weight management clinic is now seeing a lot more patients with obesity-related diseases. He added: “We are seeing more severe levels of obesity and and we are seeing more severe complications.”So in order to be able to pick that up we need to have good measures that tell us more about people’s health.”Between 2019-2020 and 2020-2021, the proportion of overweight and obese Year 6 primary school children, aged between 10 and 11, went from 35.2% to 40.9%, with people from deprived areas disproportionately affected.Researchers used BMI data from the government’s National Child Measurement Programme, which weighs and measures about a million Year 6 pupils annually in England.Body Mass Index (BMI) has long been the go-to tool for determining a healthy weight. It’s a simple and quick way to check and is a measure of body fat based on height and weight.However, many health practitioners now use the waist-to-height ratio method in addition. This is because BMI doesn’t take into account a person’s body frame or muscle mass.However, this scale has recently been called outdated by some groups as it would place a rugby player, for example, in the obese category.Researchers from the University of Bristol, the University of Exeter, and the University of Eastern Finland have found one option that could replace BMI, and said that it can more accurately measure excess fat mass in children and adolescents.Lead author, Professor Andrew Agbaje said that the waist circumference-to-height ratio is an inexpensive way to determine excess fat mass and distinguish muscle mass from fat mass. Professor Agbaje added: “With just a measuring tape we can dictate eight out of ten children who are truly fat and the second thing is we can also detect 93 out of 100 who are not fat at all, who are just muscular.”So we can detect 93 of those people who are not truly fat whom BMI would have judged had been overweight and obese as not having a problem with fat at all.”He said that BMI varies with age and sex, but waist-to-height ratio stays the same irrespective of age and sex.Follow BBC Bristol on Facebook, X and Instagram. Send your story ideas to us on email or via WhatsApp on 0800 313 4630.More on this storyPandemic obesity in kids could be lifelong – studyPublished24 JanuaryRelated Internet LinksStudy details from Paediatric ResearchThe BBC is not responsible for the content of external sites.

Reality TV star Vicky Pattison had some of her eggs frozen last year. She told the BBC that she plans to donate any she doesn’t use, to help couples who are struggling to conceive naturally.UK viewers can watch Egg Freezing and Me on BBC iPlayer now.

U.S. veterans of the wars in Afghanistan and Iraq who suffered mild traumatic brain injury from exposure to explosive blasts were found to have changes in cerebrospinal fluid proteins that are typically seen in people who develop Alzheimer’s disease, according to researchers at the University of Washington School of Medicine and VA Puget Sound Health Care System.
“While our research does not prove that veterans who experienced these injuries will develop Alzheimer’s disease, it raises the possibility that they may be on a pathway leading to dementia,” said Dr. Ge Li, the paper’s first author and an associate professor of psychiatry and behavioral sciences at UW Medicine.
The study was published March 13 in the journal Neurology.
Previous research has found that sustaining a moderate to severe TBI increases a person’s risk of developing Alzheimer’s disease. It is not known, however, whether a mild TBI (mTBI) similarly increases this risk.
In the new study, the researchers analyzed protein levels in spinal fluid from 51 U.S. veterans of the wars in Afghanistan and Iraq. Each had suffered mTBIs from exposure to explosive blasts and had an average of 20 blast injuries. Those protein levels were compared with the protein levels of 85 veterans and civilians of similar age who had never sustained a TBI.
In this study, the veterans were considered to have experienced a TBI if they had an alteration or loss of consciousness from the blast. The TBIs were considered mild if the loss of consciousness lasted 30 minutes or less and there was no sign of brain damage on standard clinical MRI or CT scan. Such an injury is considered equivalent to a concussion.
The researchers examined protein levels in the veterans’ cerebrospinal fluid, which flows around and through the brain and carries away waste materials. Two of the proteins measured compose the chief components of amyloid plaques, which aggregate in the brains of people with Alzheimer’s. These proteins are called alpha-beta amyloid 40 and 42 (Aβ40, Aβ42).

The other proteins are versions of the tau protein. Normally, tau proteins are part of cells’ cytoskeletons, which give cells their shape. But with Alzheimer’s, these structures are changed, creating tangles within brain cells and killing them. This is the other hallmark of Alzheimer’s.
With Alzheimer’s disease, the levels of alpha-beta amyloid proteins in spinal fluid typically decrease. Researchers hypothesize that the proteins, instead of being flushed out into the spinal fluid and carried away as they normally would be, are deposited in amyloid plaques and remain in the brain. As the disease progresses, tau levels, in contrast, tend to be higher than normal, as the proteins are released from dying brain cells.
In the study, mTBI veterans in their late 40s and 50s had lower levels of beta-amyloid proteins, compared with the veterans and civilians who had not had such injuries.
Tau protein levels also were abnormal in the older mTBI veterans. Normally, tau levels rise as we age. But among the older middle-aged mTBI veterans, levels tended to remain the same, a finding that the normal brain clearance system may not be working as well in among the people with mTBI.
Among older mTBI veterans, having lower beta-amyloid 42 levels was also associated with doing less well on cognitive tests assessing verbal memory and fluency.
The decline in beta-amyloid proteins, in particular beta-amyloid 42, was concerning, said senior author Dr. Elaine Peskind, a UW research professor of psychiatry and director of the VA’s Northwest Mental Illness Research, Education, and Clinical Center.
“A decline in beta-amyloid 42 is the earliest detectable change due to Alzheimer’s that can be found in a cognitively normal person,” she said. “The change can appear as much as 20 years before symptoms. So a person can have the pathology of Alzheimer’s going on in their brain but still not have any symptoms — no problem with their memory or thinking functions — for as long as 20 years.”
Peskind and her collaborators suspect the cause of the changes in the mTBI veterans’ spinal fluid proteins is due to blast-related damage to a system in the brain, called the glymphatic system, that allows fluids to flow through the brain and carry away waste products. To find out, they have been funded by the National Institute of Neurological Diseases and Stroke to study the regulation and function of this system in veterans with these injuries.